Following vasectomy, sperm and spermatogenic cell antigens, escaping the blood-testis barrier, elicit an autoimmune response in men. With the exception of the defined nuclear protamines, the chemical nature of human sperm autoantigens remains unknown. The aim of this proposal is to produce hybridomas from human peripheral lymphocytes harvested during the post-vasectomy autoimmune response. The HGPRT- human myeloma line GM 1500-6TG-AL-2 will be utilized in human X human cell fusions; for the purpose of establishing stable hybridomas, from which human monoclonal antibody, recognizing human sperm autoantigens, will be harvested and purified. A combination of biochemical, immunological, immunocytochemical, and ultrastructural approaches with human monoclonal antibody probes will then be utilized to: 1) Characterize protein, glycoprotein or glycolipid sperm surface autoantigens; 2) Characterize protein or glycoprotein sperm cytoplasmic autoantigens; 3) Immunohistochemically map the topographical distribution of surface and cytoplasmic autoantigens; 4) Establish a radioimmunoassay of autoantigens in blood, seminal plasma, and tissue extracts. It is expected that information derived from these studies will provide a better understanding of the character of the antibody response to sperm autoantigens and of the chemical nature of these autoantigens, and may serve as a basis for identifying potential immunogenic determinants for contraceptive vaccines, or avenues for immunological therapy of immune infertility.